Article
Wang and Hou
(4R,5R,6R)-4,5-bis(benzyloxy)-6-(methoxymethoxy)oct-
7-enoic acid (11)
lyst, 2nd generation (3.7 mg, 4.3 mmol) in dichloromethane
(44 mL) was placed in a reaction tube, sealed and heated in
a 60 ºC oil bath for 16 h. The crude lactone (48 mg) was
harvested after concentrated. 1H NMR (CDCl3, 300 MHz)
d 1.20-1.42 (m, 17H), 1.95-2.19 (m, 4H), 2.29-2.58 (m,
2H), 3.36 (s, 3H), 3.64-3.73 (m, 1H), 3.81-3.86 (m, 1H),
4.11-4.26 (m, 1H), 4.33-5.05 (m, 7H), 5.28-5.43 (m, 1H),
5.77-5.89 (m, 1H); HRMS (FAB) calcd for [M+H]+
(C34H48O6) 552.3451 found 552.3458. The crude lactone
(117 mg, 0.212 mmol) was added to the suspension of pal-
ladium on charcoal (10% wt, 32 mg) and ethyl acetate/
methanol/triethylamine (50:50:1, 16 mL). The reaction
mixture was stirred for 1 h under hydrogen atmosphere, fil-
tered and concentrated to give the saturated lactone (115
mg). [a] 2D0 +56.9 (c 0.80, CHCl3); 1H NMR (CDCl3, 300
MHz) d 0.85-1.68 (m, 23H), 1.81-2.05 (m, 2H), 2.40-2.46
(m, 2H), 3.34 (s, 3H), 3.49-3.80 (m, 3H), 4.39-4.96 (m,
7H), 7.22-7.34 (m, 10H); HRMS (ESI) calcd for [M+Na]+
(C34H50O6Na) 577.3505, found 577.3507. A solution of the
saturated lactone (115 mg, 0.21 mmol) in THF (2.5 mL)
was added to the solution of LDA (0.83 mmol) in THF (2.5
mL) at -78 ºC dropwise. The solution was stirred for 1 h and
added with diphenyl diselenide (226 mg, 0.73 mmol) and
HMPA (90 ml) at -78 ºC. The reaction mixture was stirred
for another 1.5 h at -40 ºC, warmed to rt, quenched with sat.
NH4Cl(aq) (5 mL), diluted with water (5 mL), extracted with
ether (5 mL ´ 3). The combined organic layers were dried
(Na2SO4), filtered and concentrated. The residue was
redissolved in dichloromethane (2 mL). Pyridine (32 mL,
0.39 mmol) and hydrogen peroxide (35% in water, 48 mL,
1.58 mmol) was added to the solution at 0 ºC and stirred for
1 h. The reaction mixture was stirred for another 16 h at rt,
quenched with water (2 mL). The organic layer was sepa-
rated, dried (Na2SO4), filtered and concentrated. The crude
product was purified by column chromatography (SiO2,
EtOAc/hexanes, 1:9; Rf 0.36) to give 12 as a light yellow
oil (46 mg, 0.083 mmol, 40%, three steps). [a] 2D0 -3.92 (c
0.50, CHCl3); 1H NMR (CDCl3, 300 MHz) d 1.24-1.57 (m,
23H), 3.29 (s, 3H), 3.44-3.49 (m, 1H), 3.80 (dd, J = 1.2 Hz,
6.9 Hz, 1H), 4.16 (d, J = 5.7 Hz, 1H), 4.32-4.93 (m, 6H),
5.01-5.07 (m, 1H), 6.01 (dd, J = 0.6 Hz, 15.9 Hz, 1H), 6.12
(dd, J = 8.7 Hz, 15.9 Hz, 1H); 13C NMR (CDCl3, 75 MHz) d
20.4, 23.4, 25.2, 26.1, 26.6, 26.9, 27.4, 28.0, 28.1, 31.0,
35.3, 55.9, 70.6, 71.0, 74.3, 79.2, 84.1, 97.7, 125.3, 127.5,
127.8, 128.2, 128.3, 138.1, 138.7, 144.0, 165.4; HRMS
(ESI) calcd for [M+Na]+ (C34H48O6Na) 575.3349, found
575.3351.
A solution of 10 (270 mg, 0.535 mmol), lithium hy-
droxide (64 mg, 2.68 mmol) in acetonitrile (36 mL) and
water (9 mL) was stirred for 16 h at rt. The reaction mixture
was acidified with sat. NH4Cl(aq), extracted with diethyl
ether (5 mL ´ 3). The organic layers were combined, dried
(Na2SO4), filtered and concentrated. The crude product
was purified by column chromatography (SiO2, EtOAc/
hexanes, 1:1; Rf 0.41) to give 11 (182 mg, 0.44 mmol, 82%)
as a colorless oil. [a] 2D0 +3.63 (c 1.04, CHCl3); 1H NMR
(CDCl3, 300 MHz) d 1.95-2.16 (m, 2H), 2.44-2.50 (m, 2H),
3.38 (s, 3H), 3.64-3.69 (m, 1H), 3.73-3.76 (m, 1H), 4.24, (t,
J = 7.5 Hz, 1H), 4.45-4.80 (m, 6H), 5.29-5.39 (m, 2H),
4.76-5.88 (m, 1H); 13C NMR (CDCl3, 75 MHz) d 24.7,
30.0, 55.6, 71.5, 74.6, 78.0, 78.2, 81.5, 94.2, 118.9, 127.5,
127.6, 127.9, 128.2, 128.3, 135.0, 138.0, 138.5, 179.4;
HRMS (FAB) calcd for [M+H]+ (C24H31O6) 415.2116,
found 415.2121.
(4R,5R,6R)-((S)-pent-4-en-2-yl)-4,5-bis(benzyloxy)-6-
(methoxymethoxy)oct-7-enoate (3)
A solution of 11 (300 mg, 0.724 mmol), in THF (5
mL) was added with triethylamine (121 mL, 0.87 mmol)
and 2,4,6-trichlorobenzyl chloride (136 mL, 0.87 mmol),
and stirred for 1 h at rt. This solution was added into a solu-
tion of alcohol 5 and 4-dimethylaminopyridine (442 mg,
3.62 mmol) in toluene (27 mL). The reaction mixture was
heated to reflux for 2 h, cooled to rt, quenched with sat.
NaHCO3(aq) (15 mL), extracted withethyl acetate (10 mL ´
3). The organic layers were combined, dried (Na2SO4), fil-
tered and concentrated. The crude product was purified by
column chromatography (SiO2, EtOAc/hexanes, 1:9; Rf
0.42) to give 3 (404 mg, 0.70 mmol, 80%) as a light yellow
1
oil. [a] 2D0 +4.88 (c 1.01, CHCl3); H NMR (CDCl3, 300
MHz) d 1.21 (d, J = 6.3Hz, 3H), 1.26-1.38 (m, 14H), 2.01-
2.11 (m, 4H), 2.41-2.47 (m, 2H), 3.38 (s, 3H), 3.65-3.70
(m, 1H), 3.71-3.74 (m, 1H), 4.25 (t, J = 6.9 Hz, 1H), 4.47-
4.80 (m, 6H), 4.84-5.05 (m, 3H), 5.29-5.40 (m, 2H), 5.78-
5.90 (m, 2H); 13C NMR (CDCl3, 75 MHz) d 19.9, 25.0,
25.4, 28.8, 29.0, 29.4, 29.6, 30.6, 33.7, 35.9, 55.6, 70.8,
71.6, 74.6, 77.9, 78.5, 81.8, 94.3, 114.1, 118.7, 127.4,
127.6, 127.8, 127.9, 128.2, 128.3, 135.1, 138.3, 138.6,
139.1, 170.3; HRMS (FAB) calcd for [M+H]+ (C36H52O6)
580.3764, found 580.3755.
(5R,6S,7R,18S,E)-5,6-bis(benzyloxy)-7-(methoxymeth-
oxy)-18-methyloxacyclooctadec-3-en-2-one (12)
Asolution of 3 (50 mg, 0.086 mmol) and Grubbs cata-
392
© 2012 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J. Chin. Chem. Soc. 2012, 59, 389-393